Inadequacy of High-Dose Fluconazole Monotherapy Among Cerebrospinal Fluid Cryptococcal Antigen (CrAg)-Positive Human Immunodeficiency Virus-Infected Persons in an Ethiopian CrAg Screening Program

Abstract

A total of 817 human immunodeficiency virus-infected Ethiopians with CD4 <150 cells/mL underwent plasma cryptococcal antigen (CRAG) screening. CRAG prevalence was 6.2%. Of participants with plasma CRAG titers >1:640, 96% (27 of 28) had cryptococcal meningitis (cerebrospinal fluid CRAG-positive) whereas 50% (7 of 14) with 1:160-1:320 titers had meningitis. With fluconazole 1200 mg/d therapy, 68% of meningitis patients (23 of 34) died within 3 months. Plasma CRAG titers >1:160 predict meningitis, requiring more intensive antifungal therapy.

Keywords: Cryptococcal meningitis /PC; Cryptococcosis /PC; Cryptococcus; Ethiopia; Fluconazole; Mass Screening; Prevention & Control.

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

A, Plasma cryptococcal antigen (CrAg) by lateral flow assay (LFA) titer versus cerebrospinal fluid (CSF) CrAg positivity. In 5 patients who declined lumbar puncture (LP), CSF results were imputed based on clinical symptoms. Two patients were asymptomatic with plasma titers ≤1:80, and 3 had symptomatic meningitis with headache (n = 3) and/or altered mental status (n = 2). Among patients with plasma CrAg titers from 1:160 to 1:640, 65% (13 of 20) were CSF positive, including 7 of 8 with a titer of 1:640. B, Matrix plot of CD4+ T-cell count versus plasma CrAg titer and CSF positivity or negativity.